Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning

Abstract

Associative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum, but its mechanism remains controversial. EBCC involves a sequence of learning processes which are thought to occur in the cerebellar cortex and deep cerebellar nuclei. Recently, the extinction phase of EBCC has been shown to be modulated after one week by cerebellar continuous theta-burst stimulation (cTBS). Here, we asked whether cerebellar cTBS could affect retention and reacquisition of conditioned responses (CRs) tested immediately after conditioning. We also investigated a possible lateralized cerebellar control of EBCC by applying cTBS on both the right and left cerebellar hemispheres. Both right and left cerebellar cTBSs induced a statistically significant impairment in retention and new acquisition of conditioned responses (CRs), the disruption effect being marginally more effective when the left cerebellar hemisphere was stimulated. These data support a model in which cTBS impairs retention and reacquisition of CR in the cerebellum, possibly by interfering with the transfer of memory to the deep cerebellar nuclei.

Frequency-dependent modulation of cerebellar excitability during the application of non-invasive alternating current stimulation

“…Previous work has employed techniques such as rTMS and tDCS with the intention to produce long-lasting excitability changes to cerebellar function [18,37,45,46]. These techniques are thought to modulate the activity of Purkinje cells, which exhibit bi-directional plasticity that are critical for fine movement control and learning of motor skills.…”

Computational Modelling of Cerebellar Magnetic Stimulation: The Effect of Washout

“…Monaco and colleagues [13,14] have employed TMS stimulation on human participants between two sessions of eyeblink conditioning protocol (EBC), a temporal associative task in which the subject learns, thanks to cerebellar plasticity, the precise timing associations between two stimuli. In EBC, the participant learns the association between a neutral conditioned stimulus (e.g., a sound) and a following unconditioned stimulus, eliciting an eyeblink (e.g., an electric shock near the eye).…”

“…The two EBC studies [13,14] have common features, such as the presence of two consecutive sessions of EBC (session 1 and session 2 ), each one composed of 6 blocks of acquisition, where two stimuli were provided to the subject, and one block of extinction, where only one stimulus was provided to the subject. In the acquisition phase, the subject learns the timing association between the two stimuli, thus exhibiting an increasing percentage of correct CRs.…”

Dynamic Redistribution of Plasticity in a Cerebellar Spiking Neural Network Reproducing an Associative Learning Task Perturbed by TMS

“…The computational protocol aimed to reproduce the experimental protocol defined by Monaco and colleagues. 14 Thirty six right-handed healthy subjects participated in this study (21 females and 15 males, mean age 28.6 ± 3.2). Informed consent was obtained from all participants, and the study was approved by the local Ethics Committee and conducted in accordance with the regulations laid down in the Declaration of Helsinki.…”

“…In both cases, TMS was applied just after the first training session, but clearly the two conditions were different in terms of consolidation times. 14 The EBCC data can be mechanistically interpreted through models embedding a well-defined set of learning mechanisms into a detailed cerebellar neural network. A cerebellar spiking neural network (SNN), [15][16][17][18] equipped with distributed plasticity mechanisms, 19,20 was indeed able to translate microcircuit operations occurring over multiple time-scales into the EBCC learning phases, 10,21 reproducing fast acquisition of time-locked motor responses, fast extinction (EX) and memory consolidation.…”